tbuckley/cabot-search huggingface dataset:
PB2229: A PHASE 3 STUDY EVALUATING THE EFFICACY AND SAFETY OF BENRALIZUMAB IN PATIENTS WITH HYPEREOSINOPHILIC SYNDROME
Authors: Princess Ogbogu, Amy Klion, Florence Roufosse, Praveen Akuthota, Paneez Khoury, Vivian Shih, Dianne Griffis, Himanshu Parikh, Ron Chen, Ying Fan, Gaell Mayer, Priya Jain, Rohit Katial, Ioannis Psallidas
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Hypereosinophilic syndromes (HES) are rare and heterogenous disorders characterized by persistent blood eosinophilia (absolute eosinophil count [AEC] >1500 cells/μL) and eosinophil-mediated end-organ involvement, including but not limited to dermatologic, pulmonary, gastrointestinal, and cardiovascular manifestations, impacting quality of life. Current treatment of symptomatic HES includes corticosteroids and corticosteroid-sparing agents. Patients often experience treatment-limiting or intolerable adverse effects despite available therapies and needed additional therapeutic options. Benralizumab is a humanized, afucosylated, anti–interleukin-5 receptor α monoclonal antibody that induces rapid, near-complete depletion of eosinophils through antibody-dependent cell-mediated cytotoxicity. Benralizumab has demonstrated corticosteroid-sparing effects in patients with severe eosinophilic asthma and AEC reductions in patients with HES. Aims: The phase 3 NATRON study (NCT04191304) will evaluate the efficacy and safety of benralizumab versus placebo in HES. Methods: This phase 3, multicenter, randomized, double-blind, placebo-controlled study (NATRON; NCT04191304) evaluating efficacy of benralizumab versus placebo will enroll ~120 participants with documented HES. Eligible participants are ≥12 years of age with an AEC ≥1000 cells/μL at screening, have signs/symptoms of an HES worsening/flare or a history of ≥2 HES worsenings/flares within 12 months prior to enrollment, and are on a stable treatment regimen (≥4 weeks). Participants must be FIP1L1::PDGFRA-negative and corticosteroid-responsive. Primary endpoint is time to first HES worsening/flare. Secondary endpoints include (but are not limited to) the proportion of participants who experience HES worsening, HES flares, and corticosteroid use during the 24-week double-blind treatment period. Participants completing the double-blind period will continue with active treatment in the setting of a ≥52-week open-label extension. Results: N/A Summary/Conclusion: These phase 3 placebo-controlled NATRON study results will characterize the efficacy and safety of benralizumab added to background therapy in patients with HES. Keywords: Hypereosinophilic syndrome, Clinical trial, Monoclonal antibody
PB2222: DOES LUNG LESION SEVERITY AFFECT THE OUTCOME IN PEDIATRIC PULMONARY MULTISYSTEM LANGERHANS CELL HISTIOCYTOSIS?
Authors: Mohamed Sedky Sedky, Seham Gohar, Asmaa Salama, Iman Zaky, Omayma Hassanain, Alaa Elhaddad
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Pulmonary involvement in pediatric multisystem Langerhans cell histiocytosis (PPM LCH) might be associated with either low risk (RO-) or high risk (RO+) organs. The nodulo-cystic lung lesions although pathognomonic, are very variable in severity and remain a source of controversy in certifying pulmonary LCH diagnosis. Aims: We examined the prognostic value of clinico radiological lung lesions severity in a single center large cohort. Methods: It is a retrospective study of 350 LCH patients registered from 2007 till 2020. Severe radiological lung associated a triad of bilateral, extensive and diffuse lesions Results: Sixty-seven PPM LCH patients were included (19.1%). Of them, severe lung lesions n=24. The median follow-up was 5.6 years (IQR: 3.4 to 8.3). Their 5-year overall survival (OS) and event free survival (EFS) were 89 % and 56.6 % respectively. The EFS, for severe radiological lesions 38 % ± 20.7 versus mild 66 % ± 16.2 p 0.002, for concordant chest CT positive/ X ray positive lesions 27 % ± 22.344 versus discordant CT positive/XR negative 66 % ± 14.7 p 0.001, for clinical respiratory distress 13% ± 13.9 versus none 62% ± 22.9 p <0.001, for RO- with severe lung lesions 47% ± 30.4 versus RO- without severe lung 69% ± 5.9 p0.04. There was a tendency for the independent prognostic impact of severe lung involvement; aHR = 1.7 (95% CI: 0.92 to 3.13, p=0.09). Summary/Conclusion: Although the lung is a low -risk organ per se in LCH, our study demonstrates a non negligeable prognostic impact of severe lung involvement in the risk stratification of pediatric LCH. This warrants further study and external validation. Keywords: Lung, Pediatric, Langerhans Cell Histiocytosis, Pulmonary
PB2148: IMPACT OF OBESITY IN THE CLINICAL OF MULTIPLE MYELOMA PATIENTS: A REPORT FROM MMRF DATASET
Authors: Liang Ren, Peng Liu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Obesity is a risk factor for multiple myeloma (MM), as increased incidence and mortality were observed in obese MM patients. However, we are still shortage of knowledge of the clinical course of obese MM patients in a broad view. Aims: In this study, we tried to portray the full aspects of obese MM patients. Methods: Here, we reviewed MM patients recorded in the MMRF CoMMpass dataset(IA18). Patients were divided into normal and obese groups according Body Mass Index (BMI) at diagnosis(normal, 18.5≤BMI<25; obese, BMI≥30), then the baseline characteristics, cytogenetic abnormalities, treatment variability, and survival outcomes were evaluated in the obese cohort. Results: 568 MM patients who met the eligibility criteria for inclusion were studied, of whom 254 patients were grouped in normal category, the rest 314 were assigned as obese MM patients. The median follow-up time was 70.5 months (range, 1.5-98.7 months). We found no differences of baseline characteristics when comparing normal and obese MM patients other than more male in the obese part (50.4% vs 59.9%, P =0.024). The overall distribution of cytogenetics abnormalities did not show some specific favor between two groups. We also found obese MM patients had a higher Object response rate (ORR) compared with normal BMI patients (92.7% vs 88.6%, P =0.037). Additionally, obese patients seemed to need shorter time or less cycles to achieve best response with first-line therapy. Compared with the normal BMI MM patients, the Progression- free survival (PFS) made no difference in the obese group (P =0.88). Median overall survival (OS) was shorter for obese MM patients but without significant meaning (82.3 vs 95.3 months, P =0.25). However, in the subgroup analysis, MM patients younger than 65 years who were obese had significantly inferior OS than that in the normal category (P =0.047, Figure 1). Summary/Conclusion: Collectively, our study indicated that obesity did not show significant prognostic value on survival of MM patients. However, young MM patients below 65 years who were obese tend to have inferior OS compared to the normal BMI group. The presence of obesity might make patients benefit more from present therapy as obese MM patients had higher ORR and responded faster.Keywords: Myeloma, Multiple myeloma, Obesity
PB1978: PATIENT-CENTREDNESS IS PIVOTAL IN A PROSPECTIVE DOSE REDUCTION TRIAL OF TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA
Authors: Melissa Djodikromo, Charlotte Bekker, Rosella Hermens, Yolba Smit, Tim Govers, Bart van den Bemt, Nicole Blijlevens
Journal: HemaSphere (2023)

Topic: 8. Chronic myeloid leukemia - Clinical Background: Dose reduction of tyrosine kinase inhibitors (TKI) for patients with chronic myeloid leukaemia (CML) can reduce adverse drug events and medication costs while maintaining therapeutic effectiveness. Aims: This study aims to develop and evaluate a patient-guided dose reduction strategy, consisting of a patient-decision aid to guide decision making and a shared decision-making consultation to discuss patient’s willingness for dose reduction and to define a personalized dose. Methods: We developed, pilot-tested and evaluated a complex intervention guided by Medical Research Council framework. Phase 1 involved intervention development based on a needs assessment using semi-structured interviews with 19 CML patients and 12 healthcare providers regarding dose reduction. In a separate iterative design process with 18 patients and 16 healthcare providers a decision aid was developed. In phase 2 the intervention was pilot-tested on acceptability, feasibility and delivery method with 6 patients and 3 healthcare providers. Phase 3 is a prospective, multicentre, single-arm trial with 147 CML patients with stable disease assessing intervention effectiveness of dose reduction on the proportion of patients with intervention failure, defined as loss of major molecular response, at 12 months after dose reduction. Secondary outcomes include validated PROMs for side effects, quality of life, medication adherence and beliefs. Interim analysis is planned for 70 patients 6-month follow-up.* Results: Patients and healthcare providers expressed a need for dose reduction and developed together a patient decision aid to guide shared decision-making. Pilot-testing showed intervention acceptance and feasible recruiting and delivery process. Currently phase 3 is ongoing in 9 Dutch hospitals, with 80 CML patients who provided consent and received a personalised TKI dose. Preliminary results showed 3/15 (20%) patients with intervention failure after dose reduction at 6-month follow-up. Summary/Conclusion: Patient-directed dose reduction using shared decision-making personalizes TKI management without loss of effectiveness. *Interim analysis data will be presented during conference Keywords: Tyrosine kinase inhibitor, Chronic myeloid leukemia, Dose escalation, Side effects
PB1945: PATIENT PERSPECTIVES ON CLL TREATMENT SIDE EFFECTS: A SUB-ANALYSIS OF THE VOICE SURVEY
Authors: Constantine Tam, Javier Pinilla-Ibarz, Volkan Karakus, Miguel Pavlovsky, Stephan Stilgebauer, Martin Šimkovič, Ana Cristina Fenili, Miguel Augusto Miroli, Carolina Garcia Castillo, Kathryn Huntley, Catherine Moura, Fernando Piotrowski, Mervat Mattar
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Treatment for chronic lymphocytic leukemia (CLL), including chemoimmunotherapy and targeted drugs, is associated with various adverse events. We surveyed patients with CLL about their knowledge and attitudes regarding treatments and “side effects” (SEs), a more widely understood term for adverse events. Aims: These results are part of a global survey of patients with CLL and were analyzed to examine patients’ knowledge, experience, and perceptions of side effects commonly associated with CLL treatment. Methods: Clinicians and patient advocacy group representatives developed and distributed a survey from March through December 2022 in 12 countries to patients with CLL who underwent ≥1 line of treatment. The anonymous survey was available via an electronic platform, digital questionnaires (.pdf), or paper forms. This sub-analysis includes items regarding SEs during treatment intervals, although the SEs queried were not comprehensive. Results: Treatment SEs had a moderate or high impact on 27%–43% of patients in every domain queried (Table). Most patients (300/370; 81%) discussed SEs with their physicians “always” or “sometimes”, but 42% (117/277) were seeking more information about the benefits and SEs associated with their treatment, primarily via the internet. When asked how they would respond to common SEs, most patients would consult their physician first. Notably, >10% of them would continue treatment normally if they experienced arrhythmias or cardiac problems, and 21% would continue if they developed hypertension (Table). A similar proportion (11%) would continue treatment if they had an infection, while 23% of them would consider stopping treatment without medical advice if they developed skin cancer. Summary/Conclusion: These results show the impacts of SEs from CLL treatment affect substantial numbers of patients in multiple life areas. The responses suggest that despite patient-physician communication about SEs, there is a need to help patients find reliable information about their treatments online as well. Finally, patients’ willingness to stop or continue treatment in the event of various SEs, including cardiovascular or oncologic events, indicates a critical knowledge gap regarding the risk associated with these events. The real-world data presented herein highlights areas in which improved patient education initiatives could directly improve patient outcomes.Keywords: Side effects, Chronic lymphocytic leukemia, Patient reported outcomes, Real world data
PB1724: NILOTINIB PLUS CHEMOTHERAPY IN PEDIATRICS WITH PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LEUKEMIA: A SINGLE CENTER EXPERIENCE
Authors: Yanming LI, Peijing Qi, Ying Wu, Wei Lin, Ruidong Zhang
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Despite significant improvements in the prognosis of dasatinib plus multi-agent chemotherapy for pediatric Philadelphia chromosome-positive (Ph-positive) acute leukaemia, there are still about 19.8% of subsequent relapses and 11.8% of disease-related deaths, which are associated with poor survival and quality of life. Moreover, dasatinib-induced side effects occur, some pediatric Ph-positive ALL patients are intolerant to standard therapy and may leukaemia progression from delaying chemotherapy. Nilotinib is a second-generation tyrosine kinase inhibitor approved by the FDA for the treatment of pediatrics with Ph-positive chronic myelogenous leukaemia. The combination of nilotinib with chemotherapy was reported effective for adults with Ph-positive ALL in phase 2 studies, but evidence of efficacy and safety among pediatrics with Ph-positive acute leukaemia is still lacking. Aims: To investigate the efficacy and safety of nilotinib (230mg/m2 twice a day) with chemotherapy in BCR-ABL1-positive or dasatinib-intolerant pediatric Ph-positive acute leukaemia patients in a real-world setting. Methods: This is a retrospective, observational study including BCR-ABL1-positive or dasatinib-intolerant pediatric patients aged < 18 years with Ph-positive acute leukaemia while complete response achieved after induction therapy during the period 2020-2023. Nilotinib was administered 230mg/m2 twice a day with standard chemotherapy. Molecular response and adverse events were assessed. The deep molecular response is defined as BCR-ABL1 values of ≤ 0.01% on the international reporting scale. Results: Eleven Ph-positive patients were included in this study with a median age of 7 (range, 2-11 years) years, including ten cases of acute lymphoblastic leukaemia and one mixed phenotype acute leukaemia. Nilotinib was applied for BCR-ABL1-positive (> 0.01%, n = 3) or dasatinib-intolerant (n = 8) cases. 8 patients discontinued dasatinib due to gastrointestinal bleeding and hydrothorax. All patients achieved deep molecular response after nilotinib-based therapy. The median follow-up time was 10.7 (range, 0.5-33.6) months and all 11 patients remained on continuation therapy. No febrile neutropenia, infection or grade ≥ 3 non-hematologic adverse events occurred when nilotinib administered. Summary/Conclusion: Our study evaluated the use of nilotinib in combination with chemotherapy in pediatrics with Ph-positive acute leukaemia. These promising results suggest nilotinib based therapy was safe and resulted in deep molecular responses in pediatric Ph-positive acute leukaemia with BCR-ABL1-positive and dasatinib intolerance, although long-term follow-up is still needed.Keywords: Nilotinib, Philadelphia chromosome, Acute leukemia, Pediatric
PB1836: LOSS OF HETEROZYGOSITY IN AML PATIENTS WITH INV(16)
Authors: Dmitry Bessmertniy, Zalina Fidarova, Irina Lukyanova, Natalia Risinskaya, Andrey Sudarikov
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Genomic instability associated with high mutation frequency, can affect cell cycle regulation and immunological control of tumor growth. Two mechanisms of the loss of heterozygosity (LOH) are described: quantitative loss of alleles (CL-LOH) and copy neutral: duplication of the alleles containing oncogenic mutations (CN-LOH). LOH can be found in different hematopoietic malignancies, although it’s quite rare in patients with acute myeloid leukemia (AML). Aims: To measure LOH occurrence in tumor cells of patients with inv(16) AML. Methods: Our retrospective study included 14 patients with de novo inv(16) AML, and one patient with relapse of inv(16) AML. All patients received treatment in the National Medical Research Center for Hematology (Moscow, Russia) from 2017 to 2023. Median of age was 36 years, M:F ratio = 8:7, extramedullary involvement (neuroleukemia) had 7 out of15 patients (47%). Two patients were diagnosed with AML during pregnancy, one case was associated with the previous treatment. All patients received “7 + 3” as an induction course (cytarabine 200 mg/m2 days 1-7, daunorubicin 60 mg/m2 days 1-3). As a study material we used tumor DNA, extracted from bone marrow sample during primary diagnosis. Control DNA was extracted from bone marrow sample after achieving complete remission (morphological, immunophenotypical) or from buccal epithelium. Standard cytogenetic study (20 metaphases) and FISH analysis (200 metaphases) were performed on every primary specimen. DNA microsatellite amplification (short tandem repeat, STR) was used for the detection of additional aberrations (CN-LOH). We used COrDIS PLUS diagnostic panel (LLC Gordiz, Russia), which includes 19 STR markers: D1S1656, D2S441, D3S1358, D5S818, D7S820, D8S1179, D10S1248, D12S391, D13S317, D16S539, D18S51, D21S11, D22S1045, CSF1PO, FGA, SE33, TH01, TPOX, VWA. STR loci were amplified in polymerase chain reaction (PCR). Subsequently fragment analysis of PCR products was performed with Nanophor – 05 genetic analyzer (LLC Syntol, Russia). Results: All patients achieved complete remission (morphological and immunophenotypical) after first course of chemotherapy. STR results are present in figure 1. LOH was found in 3/15 patients (20%): two had LOH on D10S1248, and one had LOH on D12S391. These three patients still remain in complete remission: two of them are still receiving treatment (supportive therapy and consolidation), third patient was withdrawn from treatment September 2021. Summary/Conclusion: The data obtained suggest that LOH may not be associated with the tumor transformation in de novo inv(16) AML. LOH found in these three patients was not associated with the disease outcome. Further characterization of LOH in AML might require array comparative genomic hybridization (aCGH).Keywords: Inv(16), LOH, Acute myeloid leukemia
PB1964: COMPARISON OF CLINICO-HEMATOLOGICAL PARAMETERS AND MOLECULAR AND CYTOGENETIC RESPONSE OF TWO BCR-ABL FUSION TRANSCRIPTS IN CHRONIC MYELOID LEUKEMIA TREATED WITH IMATINIB
Authors: Laabidi Baraa, Slama Nader, Ouahchi Ines, Wiem Boufrikha, Adnene Laatiri
Journal: HemaSphere (2023)

Topic: 7. Chronic myeloid leukemia - Biology & Translational Research Background: Chronic Myeloid Leukemia is (CML) characterized by Philadelphia chromosome resulting in the fusion between the BCR gene, located on chromosome 22, and the ABL gene on chromosome 9, giving rise to a fusion gene called BCR-ABL. Most patients (95 %) were found to have rearrangement in the M-BCR region in the BCR gene and thus gives rise to b2a2 or b3a2 variants. Aims: The aim of this study was to determine the prognostic impact of the different subtypes of BCR-ABL transcript on clinical, hematological, molecular and cytogenetic parameters of our study population and to evaluate the outcome of CML patients treated with Imatinib with these transcripts. Methods: This study included newly diagnosed chronic phase CML patients and was conducted in the Hematology Department of Fattouma Bourguiba University Hospital of Monastir, Tunisia, during the period between February 2003 and April 2022. Results: We enrolled 73 patients. The median age of our population was 50 years with a slight female predominance (sex-ratio 0.78). Sixty percent had the b3a2 type BCR-ABL, 34% had the b2a2 type, and 6% had the co-expression of two transcripts (b3a2+b2a2). Patients with b3a2 subtype showed higher total leukocyte count (p=0.4; Odds Ratio (OR)=1.68), and was associated significantly with thrombocytosis (p=0.006; OR=4.64) compared to those with b2a2 transcript. A high Sokal score was significantly associated with b3a2 transcript (p=0.001; OR=9.5). The two transcripts isolated were not significantly associated with sex, age group, blast cell percentage or the identified ranges of spleen size. In analyzing the therapeutic response, the proportion of patients with b3a2 achieving complete cytogenetic response at 12 months is higher compared with b2a2 patients (89% vs 41%). This difference is statistically significant (p=0.001; OR=9.5). Molecular response at 3 months (BCR-ABL≤10%) and major molecular response at 12 months were found to have a significant association with b3a2 transcript, p value is 0.04 and 0.004, respectively. Our study concluded that b2a2 transcript is a prognostic factor in cytogenetic and molecular response with an OR equal to, respectively, 9.5 and 4.89. Summary/Conclusion: The significant findings of our study were the association of b3a2 with thrombocytosis and cytogenetic and molecular response. Therefore, these findings need further studies and validation. Keywords: Chronic myeloid leukemia, Molecular response, BCR-ABL